Long-Term In Vivo Magnetic Resonance Imaging Tracking of Endothelial Progenitor Cells Transplanted in Rat Ischemic Limbs and Their Angiogenic Potential

: Agudelo CA, Tachibana Y, Noboru T, Iida H, Yamaoka T

Publisher: MARY ANN LIEBERT, INC

: 2011

: Tissue Engineering: Parts A, B, and C

: TISSUE ENGINEERING PART A

: TISSUE ENG PT A

: 17

: 15-16

: 2079

: 2089

: 11

: 1937-3341

DOI: https://doi.org/10.1089/ten.tea.2010.0482

Stem cell therapy has been used to repair ischemic tissues in the limbs, in myocardial infarctions, and in the brain. To understand the mechanisms of healing, a contrast agent capable of inducing sufficient magnetic resonance (MR) contrast would be useful in providing fundamental information about the cell migration and incorporation into the ischemic tissue. A magnetic resonance imaging contrast agent composed of dextran and gadolinium chelate was synthesized. Hydroxyl groups of dextran were activated with 1,1'-carbonylbis-1H-imidazole and reacted with propanediamine to obtain aminated dextran. This modified polymer was then reacted with mono-N-succinimidyl 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate, then with fluorescein isothiocyanate, and finally reacted with gadolinium chloride solution (Dex-DOTA-Gd3(+)). Endothelial progenitor cells (EPCs) were selected as a stem cell model for magnetic resonance imaging tracking. Cells were isolated from the bone marrow harvested from the femurs and tibias of rats. Dex-DOTA-Gd3(+) was then introduced into the EPCs by electroporation. The intracellular stability and cytotoxicity of Dex-DOTA-Gd3(+) were evaluated in vitro. Dex-DOTA-Gd3(+)-labeled EPCs were transplanted into a rat model of ischemic limb, and MR images were acquired. Dex-DOTA-Gd3(+) was found to efficiently label EPCs over a long duration without significant cytotoxicity. This provides an MR signal sufficient for tracking the EPCs intramuscularly injected into the limb.